Treatment of Inflammatory Disorders

Abstract

Modulation of the neural activity of a nerve adjacent to the left gastro epiploic artery (LGEA) and/or a nerve adjacent to a short gastric artery (SGA) can modulate the neural activity of the sympathetic nerves that impact splenic function. This is useful for reducing inflammation and providing ways of treating inflammatory disorders.

1 - 27 . (canceled) 
     
     
         28 . A system for modulating neural activity in a subject's nerve adjacent to a left gastro epiploic artery (LGEA) and/or a subject's nerve adjacent to a short gastric artery (SGA), the system comprising:
 at least one electrode, in signaling contact with the nerve; and   a voltage or current source configured to generate at least one electrical signal with a charge density to be applied to the nerve via the at least one electrode such that the charge density per phase applied to the nerve by the electrical signal is between 5 μC per cm 2  per phase to 150 μC per cm 2  per phase, wherein the electrical signal comprises a pulse train having a pulse width >1 ms, and wherein the electrical signal modulates the neural activity of the nerve to produce a change in a physiological parameter in the subject,   wherein the change in the physiological parameter is one or more of the group consisting of: a reduction in a pro-inflammatory cytokine, an increase in an anti-inflammatory cytokine, an increase in a catecholamine, a change in an immune cell population, a change in an immune cell surface co-stimulatory molecule, a reduction in a factor involved in the inflammation cascade, a change in the level of an immune response mediator, a decrease in splenic blood flow, and an increase in systemic blood pressure.   
     
     
         29 . The system of  claim 28 , wherein the pulse width is ≤5 ms. 
     
     
         30 . The system of  claim 28 , wherein the pulse width is between 1.5 and 2.5 ms. 
     
     
         31 . The system of  claim 28 , wherein the pulse width is ≤3 ms. 
     
     
         32 . The system of  claim 28 , wherein the pulse train has an interphase delay of ≤0.3 ms. 
     
     
         33 . The system of  claim 32 , wherein the interphase delay is ≥0.1 ms. 
     
     
         34 . The system of  claim 33 , wherein the interphase delay is between 0.2 ms and 0.25 ms. 
     
     
         35 . The system of  claim 28 , wherein the at least one electrode has a surface area of 0.1-0.3 cm 2 . 
     
     
         36 . The system of  claim 28 , wherein the at least one electrode has a surface area of ≤0.2 cm 2 . 
     
     
         37 . The system of  claim 28 , wherein the system modulates neural activity in a nerve adjacent to the LGEA, and the at least one electrode is placed on or around both the nerve adjacent to the LGEA and the LGEA. 
     
     
         38 . The system of  claim 28 , wherein the system modulates neural activity in a nerve adjacent to the LGEA, wherein the at least one electrode is placed on or around the nerve adjacent to the LGEA. 
     
     
         39 . The system of  claim 28 , wherein the system modulates neural activity in a nerve adjacent to the SGA, and the at least one electrode is placed on or around both the nerve adjacent to the SGA and the SGA. 
     
     
         40 . The system of  claim 28 , wherein the system modulates neural activity in a nerve adjacent to the SGA, and the at least one electrode is placed on or around the nerve adjacent to the SGA. 
     
     
         41 . The system of  claim 28 , wherein the voltage or current source is configured to apply the at least one electrical signal episodically. 
     
     
         42 . The system of  claim 28 , wherein the voltage or current source is configured to apply the at least one electrical signal periodically. 
     
     
         43 . The system of  claim 28 , comprising a detector configured to:
 detect one or more signals indicative of one or more physiological parameters;   determine from the one or more signals one or more physiological parameters;   determine the one or more physiological parameters indicative of worsening of the physiological parameter; and causing the at least one electrical signal to be applied to the nerve via the at least one electrode,   wherein the physiological parameter is one or more of the group consisting of: a level of a pro-inflammatory or an anti-inflammatory cytokine, a level of a catecholamine, a level of an immune cell population, a level of an immune cell surface co-stimulatory molecule, a level of a factor involved in the inflammation cascade, a level of an immune response mediator, splenic blood flow, and systemic blood pressure.   
     
     
         44 . The system of  claim 43 , further comprising a memory configured to store data pertaining to the physiological parameters in a healthy subject, wherein determining the one or more physiological parameters indicative of worsening of the physiological parameter comprises comparing the one or more physiological parameters with the data. 
     
     
         45 . The system of  claim 28 , further comprising:
 a communication subsystem configured to receive a control signal from a controller and, upon detection of said control signal, cause the at least one electrical signal to be applied to the nerve via the at least one electrode.   
     
     
         46 . A method of reducing inflammation in a subject by reversibly modulating neural activity of the subject's nerve adjacent to an LGEA and/or the subject's nerve adjacent to an SGA, comprising:
 (i) implanting in the subject a system of  claim 28 ;   (ii) positioning the at least one electrode in signaling contact with the nerve; and   (iii) activating the system.   
     
     
         47 . A method for treating an inflammatory disorder, comprising:
 applying an electrical signal with a charge density to a subject's nerve adjacent to a left gastro epiploic artery (LGEA) and/or a subject's nerve adjacent to a short gastric artery (SGA) via at least one electrode, in signaling contact with the nerve, wherein the electrical signal comprises a pulse train having a pulse width >1 ms, wherein the charge density per phase applied to the nerve by electrical signal is between 5 μC to 150 μC per cm 2  per phase, such that the electrical signal reversibly modulates neural activity of the nerve to produce a change in a physiological parameter in the subject,   wherein the change in the physiological parameter is one or more of the group consisting of: a reduction in a pro-inflammatory cytokine, an increase in an anti-inflammatory cytokine, an increase in a catecholamine, a change in an immune cell population, a change in an immune cell surface co-stimulatory molecule, a reduction in a factor involved in the inflammation cascade, a change in the level of an immune response mediator, a decrease in splenic blood flow, and an increase in systemic blood pressure.